We all know that hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma, and that high HBV levels increase the risk of recurrence after hepatectomy for liver cancer caused by HBV infection.
It has been previously demonstrated that if aggressive postoperative antiviral therapy reduces the level of HBV DNA, the patient’s risk of liver cancer recurrence is reduced.
So, if these patients do not have high levels of HBV DNA, is it still necessary to use antivirals postoperatively? The study also found that the risk of hepatocellular carcinoma recurrence was reduced with postoperative use of antivirals. To clarify this question, the investigators conducted a well-designed prospective clinical trial.
How was this study conducted?
The study was conducted by the Shanghai Institute of Medicine.
The study was conducted jointly by the Shanghai Eastern Hepatobiliary Hospital and the Chinese University of Hong Kong, and the results were recently published in the Annals of Surgery.
This is a prospective, single-center, randomized controlled clinical trial of patients with liver cancer due to HBV infection admitted to the Eastern Hepatobiliary Hospital from November 2008 to March 2010, who were aged 18 to 70 years, had radical hepatectomy, and had low levels of HBV DNA on preoperative testing.
The patients were randomly divided into an antiviral treatment group and a control group. In the antiviral group, the antiviral drug tibivudine was started 4 to 7 days after surgery.
The primary observations of the study were progression-free survival and overall survival, with all patients followed for at least 60 months.
What are the findings of this study?
A total of 200 patients completed the study.
There were 200 patients who completed the entire trial, of whom 112 (56.0%) had tumor recurrence and 94 (47.0%) had death.
The analysis showed that for 1-, 3-, and 5-year recurrence-free survival, the antiviral group was 85.9%, 55.2%, and 52.0%, respectively, compared with 80.6%, 40.9%, and 32.3% in the control group.
For overall survival at 1, 3, and 5 years, 94.0%, 75.7%, and 64.1% were in the antiviral group versus 90.0%, 62.4%, and 43.7% in the control group, respectively.
It is clear that both relapse-free survival and overall survival were significantly better in the antiviral treatment group than in the control group without antiviral treatment.
After excluding confounding factors, further statistical analysis showed that postoperative antiviral therapy was a protective factor for late tumor recurrence, but not for early recurrence.
This result tells us that the protective effect of postoperative antiviral therapy on recurrence is mainly in advanced tumor recurrence (more than two years) and does not seem to have a preventive effect on early tumor recurrence.
What are the implications of this study for patients with liver cancer?
This study tells us that in patients with HBV infection leading to liver cancer, even if the preoperative DNA levels of HBV are low, maintaining the DNA levels of HBV at low levels after surgery can significantly reduce the risk of recurrence and death if antiviral drugs are taken.
Therefore, the investigators recommend that all patients with hepatitis B virus-induced liver cancer should receive effective antiviral therapy as soon as possible (4 to 7 days after surgery in this study) after radical hepatectomy.
This shows that for some patients with liver cancer, it is not the elevated hepatitis B virus DNA levels that require antiviral drugs.
The warning from this study is that it is important not to take for granted that “low (or undetectable) HBV does not require antivirals,” but rather to take into account the results of rigorous clinical studies and the guidance of physicians.